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Pembrolizumab Treatment in Stage III NSCLC and Alternatives

Panelists: Mark A. Socinski, MD, Florida Hospital Cancer Institute; Maximilian Hochmair, MD, Otto Wagner Spital; Suresh Senan, MRCP, FRCR, PhD, VU University Medical Center; Leora Horn, MD, MSc, FRCPC, Vanderbilt University Medical Center; Thomas E. Stinchcombe, MD, Duke University Health System
Published: Monday, Dec 17, 2018



Transcript: 

Mark A. Socinski, MD: I want to talk about pembrolizumab. I’ve heard some support that this effect isn’t specific to durvalumab [Imfinzi]. I like nivolumab [Bavencio], so I’m going to use that in this setting versus the alternative. We did have some data for pembrolizumab in a phase II trial. Can you tell us about this?

Suresh Senan, MRCP, FRCR, PhD: This was a lung group trial in which they gave concurrent chemoradiotherapy in fairly standard doses and schemes. Interestingly, they allowed the investigators to give up their 2 cycles of consolidation.

Mark A. Socinski, MD: That’s all it takes.

Suresh Senan, MRCP, FRCR, PhD: Then they restaged between 28 and 56 days and then decided in nonprogressing patients to go on with pembrolizumab for 3 weeks.

Mark A. Socinski, MD: Very different populations from the PACIFIC trial.

Suresh Senan, MRCP, FRCR, PhD: Exactly. They could continue for a year. It’s a single-arm study, and the numbers look interesting. The pneumonitis rates are what one would expect: There’s nothing to worry about. The progression-free survival 2-year control rates were impressive. It raises a lot of questions. If your patient is not eligible for the PACIFIC trial for 50 days, what should you do? Is it possible to extend that window with the PD-L1 [programmed death-ligand 1] and PD-1?

Mark A. Socinski, MD: I would use durvalumab. I wouldn’t consider any other agent in that setting.

Maximilian Hochmair, MD: With the phase III trial with durvalumab, it’s a good choice.

Mark A. Socinski, MD: We use it not only in stage III but stage IV. Is there a real difference between the PD-1 versus PD-L1 agents? That is hard to know.

Maximilian Hochmair, MD: What we know from the reviews is that the pneumonitis rate is lower with PD-L1 inhibitors with durvalumab or avelumab [Bavencio] or atezolizumab [Tecentriq]. This is a sign that you should use those.

Suresh Senan, MRCP, FRCR, PhD: The ETOP [European Thoracic Oncology Platform] trial, which we took part in, with nivolumab, had early data presented that suggested an increase with pneumonitis; we wanted to give nivolumab in this instance but had to wait for the full cohort to be analyzed of course. At this point, from a radiation toxicity point of view, I have no major concerns. We have to wait for the data, I agree with you. The randomized high-level evidence comes from durvalumab, so we should stick to it.

Mark A. Socinski, MD: As we move into early-stage disease, I’m going to ask Leora to comment on the recent study we saw with neoadjuvant nivolumab in the pathologic response rates; it was a small number of patients.

Leora Horn, MD, MSc, FRCPC: It’s promising. Patrick Ford, MD, presented the data at the American Association for Cancer Research 2018 Annual Meeting and published it in the New England Journal of Medicine. The study showed that there wasn’t a high response rate radiographically, but there was a significance among patients—40% to 50%—which showed a complete pathological response. How this translates into OS [overall survival] benefit, we’ll see in time. The other question is, if they don’t have that response, should you be administering adjuvant chemotherapy? We’re going to get those answers because there are several ongoing trials looking at neoadjuvant I-O alone or I-O with chemotherapy. There are also multiple adjuvant trials that are trying to answer the same question.

Mark A. Socinski, MD: Every I-O drug approved in stage IV disease and stage III disease is in a clinical trial in the adjuvant setting globally somewhere, right?

Leora Horn, MD, MSc, FRCPC: Absolutely.

Mark A. Socinski, MD: We have all these trials ongoing, and whether it’s neoadjuvant or adjuvant, I think we’ll have to wait for the data.

Transcript Edited for Clarity 

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Transcript: 

Mark A. Socinski, MD: I want to talk about pembrolizumab. I’ve heard some support that this effect isn’t specific to durvalumab [Imfinzi]. I like nivolumab [Bavencio], so I’m going to use that in this setting versus the alternative. We did have some data for pembrolizumab in a phase II trial. Can you tell us about this?

Suresh Senan, MRCP, FRCR, PhD: This was a lung group trial in which they gave concurrent chemoradiotherapy in fairly standard doses and schemes. Interestingly, they allowed the investigators to give up their 2 cycles of consolidation.

Mark A. Socinski, MD: That’s all it takes.

Suresh Senan, MRCP, FRCR, PhD: Then they restaged between 28 and 56 days and then decided in nonprogressing patients to go on with pembrolizumab for 3 weeks.

Mark A. Socinski, MD: Very different populations from the PACIFIC trial.

Suresh Senan, MRCP, FRCR, PhD: Exactly. They could continue for a year. It’s a single-arm study, and the numbers look interesting. The pneumonitis rates are what one would expect: There’s nothing to worry about. The progression-free survival 2-year control rates were impressive. It raises a lot of questions. If your patient is not eligible for the PACIFIC trial for 50 days, what should you do? Is it possible to extend that window with the PD-L1 [programmed death-ligand 1] and PD-1?

Mark A. Socinski, MD: I would use durvalumab. I wouldn’t consider any other agent in that setting.

Maximilian Hochmair, MD: With the phase III trial with durvalumab, it’s a good choice.

Mark A. Socinski, MD: We use it not only in stage III but stage IV. Is there a real difference between the PD-1 versus PD-L1 agents? That is hard to know.

Maximilian Hochmair, MD: What we know from the reviews is that the pneumonitis rate is lower with PD-L1 inhibitors with durvalumab or avelumab [Bavencio] or atezolizumab [Tecentriq]. This is a sign that you should use those.

Suresh Senan, MRCP, FRCR, PhD: The ETOP [European Thoracic Oncology Platform] trial, which we took part in, with nivolumab, had early data presented that suggested an increase with pneumonitis; we wanted to give nivolumab in this instance but had to wait for the full cohort to be analyzed of course. At this point, from a radiation toxicity point of view, I have no major concerns. We have to wait for the data, I agree with you. The randomized high-level evidence comes from durvalumab, so we should stick to it.

Mark A. Socinski, MD: As we move into early-stage disease, I’m going to ask Leora to comment on the recent study we saw with neoadjuvant nivolumab in the pathologic response rates; it was a small number of patients.

Leora Horn, MD, MSc, FRCPC: It’s promising. Patrick Ford, MD, presented the data at the American Association for Cancer Research 2018 Annual Meeting and published it in the New England Journal of Medicine. The study showed that there wasn’t a high response rate radiographically, but there was a significance among patients—40% to 50%—which showed a complete pathological response. How this translates into OS [overall survival] benefit, we’ll see in time. The other question is, if they don’t have that response, should you be administering adjuvant chemotherapy? We’re going to get those answers because there are several ongoing trials looking at neoadjuvant I-O alone or I-O with chemotherapy. There are also multiple adjuvant trials that are trying to answer the same question.

Mark A. Socinski, MD: Every I-O drug approved in stage IV disease and stage III disease is in a clinical trial in the adjuvant setting globally somewhere, right?

Leora Horn, MD, MSc, FRCPC: Absolutely.

Mark A. Socinski, MD: We have all these trials ongoing, and whether it’s neoadjuvant or adjuvant, I think we’ll have to wait for the data.

Transcript Edited for Clarity 
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